Physiology of the Prolactin Releasing Peptides

催乳素释放肽的生理学

• 批准号: 7583992
• 负责人: Willis K. Samson
• 金额: $ 30.6万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7583992
• 关键词: 4-nitrophenethyl bromide; Address; Antihypertensive Agents; Autonomic nervous system; Baroreflex; Behavioral; Blood Pressure; Blood Pressure Monitors; Brain; Brain Stem; Cardiovascular system; Cells; Corticotropin; Data; Development; Dopamine; Endocrine; Experimental Designs; Goals; Hormonal; Hormones; Human; Hypothalamic structure; In Vitro; Individual; Injection of therapeutic agent; Lateral; Metabolic; Metabolic syndrome; Methodology; Molecular; Neurons; Neuropeptides; Neurosecretory Systems; Nucleus solitarius; Obesity; Outcome; Peptides; Physiological; Physiology; Play; Population; Preparation; Production; Prolactin; Prosencephalon; Publishing; Rattus; Reverse Transcriptase Polymerase Chain Reaction; Role; Site; Slice; Stress; Structure of dorsomedial hypothalamic nucleus; Structure of nucleus infundibularis hypothalami; Sympathetic Nervous System; Syndrome; dorsal motor nucleus; glycemic control; hindbrain; in vivo; insight; neuropeptide B; paraventricular nucleus; prolactin-releasing peptide; research study; response; stress management; tool

DESCRIPTION (provided by applicant): This is a rerevised, competitive renewal application (HL66023) that continues our examination of the physiologic relevance of recently described neuropeptides which we have demonstrated to act at least pharmacologically to stimulate stress hormone secretion (prolactin, PRL, and adrenocorticotropin, ACTH) by a brain site of action. Additionally, these peptides stimulate stress-related behavioral responses (activity) and at least one acts in brain to stimulate sympathetic activity resulting in increased blood pressure. These peptides (prolactin releasing peptide, PrRP; neuropeptide W, NPW; and neuropeptide B, NPB) are produced in separate populations of neurons in brain, many of which innervate the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (ARC) and ventromedial and dorsomedial hypothalamic nuclei (VMH/DMH). All three peptides are contained in neurons that innervate autonomic centers in hypothalamus and brain stem. It is our goal to understand the roles these peptides play in the hypothalamic and extrahypothalamic responses to stress. We address multiple specific aims all related to the founding hypothesis that one or more of these peptides is essential for the endocrine and/or cardiovascular response to stress, under certain paradigms of stress. Our approach will be to demonstrate direct effects of these peptides on identified fore- and hindbrain neurons [e.g. in PVN, ARC, VMH/DMH, nucleus tractus solitarius (NTS), rostral lateral medulla (RVLM), and dorsal motor nucleus of the Vagus] using electrophysiologic, pharmacologic and single cell RT- PCR approaches. We will then attempt compromise of peptide production and examine hormone secretion in response to physical stress and the cardiovascular response to hypertensive and hypotensive challenge (i.e. baroreflex sensitivity). Understanding the normal mechanisms controlling the response to stress will reveal potential strategies for the management of stress in the human population and the cardiovascular and metabolic consequences of that stress. These studies may also provide insight into the central mechanisms contributing to development of the metabolic syndrome (Syndrome X), which is characterized by obesity, poor glycemic control, altered metabolic and autonomic function and a propensity for adverse cardiovascular outcomes. Additionally, these studies will provide further insight into the coordinated hormonal and autonomic responses to stress.

描述（由申请人提供）：这是一份重新修订的竞争性更新申请（HL66023），继续我们对最近描述的神经肽的生理相关性的检查，我们已经证明这些神经肽至少在药理学上可以通过大脑作用部位刺激应激激素分泌（催乳素、PRL 和促肾上腺皮质激素、ACTH）。此外，这些肽会刺激与压力相关的行为反应（活动），并且至少一种在大脑中发挥作用，刺激交感神经活动，导致血压升高。这些肽（催乳素释放肽，PrRP；神经肽 W，NPW；和神经肽 B，NPB）在大脑中不同的神经元群体中产生，其中许多神经元支配下丘脑室旁核（PVN）、弓状核（ARC）以及下丘脑腹内侧和背内侧核 （VMH/DMH）。所有三种肽都包含在支配下丘脑和脑干自主神经中心的神经元中。我们的目标是了解这些肽在下丘脑和下丘脑外应激反应中发挥的作用。我们解决了多个具体目标，所有这些目标都与以下假设相关：在某些压力范式下，这些肽中的一种或多种对于内分泌和/或心血管对压力的反应至关重要。我们的方法将是证明这些肽对已识别的前脑和后脑神经元的直接影响[例如，神经元]。使用电生理学、药理学和单细胞 RT-PCR 方法对 PVN、ARC、VMH/DMH、孤束核 (NTS)、延髓头端外侧 (RVLM) 和迷走神经背运动核进行研究。然后，我们将尝试妥协肽的产生，并检查响应身体压力的激素分泌以及对高血压和低血压挑战的心血管反应（即压力反射敏感性）。了解控制压力反应的正常机制将揭示管理人类压力的潜在策略以及压力对心血管和代谢的影响。这些研究还可以深入了解导致代谢综合征（X综合征）发展的核心机制，该综合征的特点是肥胖、血糖控制不良、代谢和自主功能改变以及不良心血管结局的倾向。此外，这些研究将进一步深入了解荷尔蒙和自主神经对压力的协调反应。